A method to quantify glucose utilization <i>in vivo</i> in skeletal muscle and white adipose tissue of the anaesthetized rat

Ferré, Pilar; Leturque, Armelle; Burnol, Anne-Françoise; Pénicaud, Luc; Girard, Jean

doi:10.1042/bj2280103

Cited by 343 publications

(275 citation statements)

References 26 publications

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“…Skeletal muscle (gastrocnemius and quadriceps) samples were removed 30 min after injection. The glucose utilisation index was determined by measuring the accumulation of radiolabelled compounds [34]. The amount of 2-DG-6-phosphate/mg protein was divided by the integral of the concentration ratio of 2-DG to unlabelled glucose measured.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice

et al. 2008

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Aims/hypothesis IL-6 is released by the adipose tissue and increased circulating levels in obesity are associated with hyperinsulinaemia and insulin resistance. Short-term experiments suggest that increased IL-6 release by the skeletal muscle following exercise may improve insulin sensitivity. Methods In order to examine the effect of chronically elevated IL-6 levels, we overexpressed Il6 in skeletal muscle in mice using an electro-transfer procedure.Results Circulating IL-6 levels were increased and the animals rapidly lost both weight and body fat, but food intake was unchanged, which is consistent with the finding that IL-6 increased energy expenditure. Insulin levels were inappropriately elevated and combined with hypoglycaemia in spite of reduced 2-deoxy-D-glucose uptake by skeletal muscle. Insulin-stimulated glucose uptake by skeletal muscles ex vivo was reduced, probably due to the decreased amounts of glucose transporter (GLUT)-4. Beta cell insulin content was increased, while apparent beta cell mass was unchanged. Circulating serum amyloid A cluster levels were increased tenfold due to a pronounced proinflammatory state in the liver with infiltration of inflammatory cells. However, no liver steatosis was found, which may be accounted for by concomitant AMP kinase activation. Conclusions/interpretation Chronically elevated IL-6 levels lead to inappropriate hyperinsulinaemia, reduced body weight, impaired insulin-stimulated glucose uptake by the skeletal muscles and marked inflammation in the liver. Thus, the pleiotrophic effects of chronically elevated IL-6 levels preclude any obvious usefulness in treating obesity or its associated metabolic complications in man, despite the fact that weight reduction may be expected.

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Section: Methodsmentioning

confidence: 99%

Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice

et al. 2008

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“…This was determined by the method of Ferre et al (1985) and found to be 0.46 in NMRI mice (Mahony and Tisdale, 1990). …”

Section: Glucose Utilization In Vivomentioning

confidence: 99%

Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentaenoic acid

Hussey

Tisdale

1999

Br J Cancer

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SummaryThe effect of a proteolysis-inducing factor (PIF), produced by cachexia-inducing tumours on glucose utilization by different tissues and the effect of pretreatment with the polyunsaturated fatty acid eicosapentaenoic acid (EPA), has been determined using the 2-deoxyglucose tracer technique. Mice receiving PIF showed a profound depression of body weight (2.3 g) over a 24-h period, which was completely abolished by pretreatment with a monoclonal antibody to PIF or by 3 days pretreatment with EPA at 500 mg kg -1 . Animals receiving PIF exhibited a marked hypoglycaemia, which was effectively reversed by both antibody and EPA pretreatment. There was an increase in glucose utilization by brain, heart and brown fat, but a decrease by kidney, white fat, diaphragm and gastrocnemius muscle after administration of PIF. Changes in organ glucose consumption were attenuated by either monoclonal antibody, EPA, or both. There was a decrease in 2-deoxyglucose uptake by C 2 C 12 myoblasts in vitro, which was attenuated by EPA. This suggests a direct effect of PIF on glucose uptake by skeletal muscle. These results suggest that in addition to a direct catabolic effect on skeletal muscle PIF has a profound effect on glucose utilization during cachexia.

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“…The correction factor for the discrimination against 2-deoxyglucose (lumped constant) does not vary with changes in glucose utilisation rates of white and brown adipose tissue, and thus the use of the GUI value gives an accurate estimation of differences between groups. 22 Conditions were near steady state with coef®cients of variance of blood glucose over the 1 h period of sampling of`15%.…”

Section: Glucose Utilisation In Vivomentioning

confidence: 99%

“…Rates of glucose uptakeaphosphorylation by adipose tissue in vivo were estimated from rates of uptake and phosphorylation of 2-deoxy[1-3 H]-D-glucose (Amersham Interanational, Amersham, Bucks, UK) 22 in unstressed conscious rats. 23 Each rat was ®tted with an indwelling cannula for injection and sampling as described in Ref.…”

Section: Glucose Utilisation In Vivomentioning

confidence: 99%

The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo

Holness

Sugden

1999

Int J Obes

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OBJECTIVE: To determine: (a) whether active pyruvate dehydrogenase (PDH a ) activity in interscapular brown adipose tissue (IBAT) is acutely regulated by altered insulin status at euglycaemia; (b) the relationship between glucose uptakeaphosphorylation and PDH a activities in IBAT in vivo; and (c) the impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in IBAT in comparison with that exerted on various white adipose tissue depots. DESIGN: Rats were provided with either a standard diet (8% fat, 72% carbohydrate, by energy) or a diet moderately high in saturated fat (47%, by energy) and low in carbohydrate (33%, by energy) for four weeks. Rats were studied in the absorptive state, in the post-absorptive state or after 2.5 h euglycaemic hyperinsulinaemia. Tissues sampled included IBAT and four white adipose tissue depots, two abdominal (parametrial (PM) and perirenal (PR)) and two super®cial (subcutaneous (SC) and interscapular (IS)). MEASUREMENTS: Whole-body glucose disposal was estimated using [3-3 H]glucose. Glucose uptakeaphosphorylation in vivo was estimated using 2-deoxy[1-3 H]-D-glucose. Insulin action was evaluated using the euglycaemic-hyperinsulinaemic clamp technique. PDH a activity was assayed spectrophotometrically in freeze-clamped tissue extracts. PDH kinase (PDK) activities were assayed in mitochondrial extracts by rates of ATP-dependent PDH a inactivation. RESULTS: Whole-body glucose disposal was decreased by high-fat-feeding in the post-absorptive state (P`0.05) and during euglycaemic hyperinsulinaemia (P`0.01). Glucose transportaphosphorylation in IBAT was decreased by highfat feeding in the absorptive (P`0.001) and post-absorptive states (by 84%, P`0.05) and during steady-state euglycaemic hyperinsulinaemia (by 73%, P`0.001). IBAT PDH a activities were suppressed by high-fat feeding. Euglycaemic hyperinsulinaemia in post-absorptive control rats increased PDH a activities in IBAT (P`0.001) to values comparable to those found in the absorptive state. Although IBAT PDH a activities were increased by euglycaemic hyperinsulinaemia in post-absorptive high-fat-fed rats, they remained lower (by 55%; P`0.01) than those of controls. The failure of hyperinsulinaemia to normalise IBAT pyruvate dehydrogenase complex (PDHC) activities in high-fat-fed rats was associated with a stable 1.4-fold increase in IBAT PDK activity. High-fat feeding decreased glucose utilisation rates in the post-absorptive state in IS, but not in SC, PM or PR white adipose tissue depots. Euglycaemic hyperinsulinaemia signi®cantly increased glucose utilisation in three out of the four depots of the control rats, but did not elicit statistically-signi®cant changes in high-fat-fed rats. High-fat feeding in¯uenced PDH a activity in PR, but was without signi®cant effect on PDH a activity in PM, SC and IS. CONCLUSIONS: The results demonstrate that PDH a activity in the IBAT of rats maintained on standard diet responds to changes in insulin concentrations over the low physiological range, and that i...

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A method to quantify glucose utilization in vivo in skeletal muscle and white adipose tissue of the anaesthetized rat

Cited by 343 publications

References 26 publications

Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice

Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice

Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentaenoic acid

The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo

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